The principal goal of the proposed research is to establish the genetic relatedness of different influenza A viruses at the level of nucleotide sequences. Specific questions that will be asked include: (1) Can the nucleotide sequence of specific genome RNA segments of past and present strains be used to map the evolutionary pathway of the present human strains? (2) Can genetic evidence be found for recombination between animal and human virus strains? (3) Does the presence of specific RNA sequence correlate with biological characteristics such as host range, virulence, or growth capacity? Genetic homologies will be measured primarily by competitive hybridization. Individual 125 iodine-labeled genome RNA segments will be annealed to homologous complementary RNA in the presence of an excess of genome RNA of other strains. The degree of inhibition of annealing will be used to determine the relatedness of corresponding RNA sequences. The above study will provide information on the origin of new epidemic and pandemic strains of influenza viruses. It may also provide us with a more rational basis on which to select future vaccine strains and formulate vaccine policies.